Document Detail

Zinc stabilizes adenomatous polyposis coli (APC) protein levels and induces cell cycle arrest in colon cancer cells.
MedLine Citation:
PMID:  15368361     Owner:  NLM     Status:  MEDLINE    
In the present study, we investigated the mechanisms by which zinc causes growth arrest in colon cancer cells. The results suggest that zinc treatment stabilizes the levels of the wild-type adenomatous polyposis coli (APC) protein at the post-translational level since the APC mRNA levels and the promoter activity of the APC gene were decreased in HCT-116 cells (which express the wild-type APC gene) after treatment with ZnCl2. Increased levels of wild-type but not truncated APC proteins were required for the ZnCl2-mediated G2/M phase arrest in different colon cancer cell lines. We further tested whether serum-stimulation, which induces cell cycle arrest in the S phase, can relieve ZnCl2-induced G2/M phase arrest of HCT-116 cells. Results showed that in the HCT-116 cells pretreated with ZnCl2, the serum-stimulation neither changed the distribution of G2/M phase arrested cells nor the increased levels of APC protein. The G2/M phase arrest correlated with retarded growth of HCT-116 cells. To further establish that wild-type APC protein plays a role in ZnCl2-induced G2/M arrest, we treated SW480 colon cancer cells that express truncated APC protein. We found that ZnCl2 treatment did not induce G2/M phase arrest in SW480 cells; however, the cell growth was retarded due to the loss of E-cadherin and alpha-tubulin levels. These results suggest that ZnCl2 inhibits the proliferation of colon cancer cells (which carry the wild-type APC gene) through stabilization of the APC protein and cell cycle arrest in the G2/M phase. On the other hand, ZnCl2 inhibits the proliferation of colon cancer cells (which carry the mutant APC gene) by disrupting cellular attachment and microtubule stability.
Aruna S Jaiswal; Satya Narayan
Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of cellular biochemistry     Volume:  93     ISSN:  0730-2312     ISO Abbreviation:  J. Cell. Biochem.     Publication Date:  2004 Oct 
Date Detail:
Created Date:  2004-09-15     Completed Date:  2005-01-06     Revised Date:  2013-02-20    
Medline Journal Info:
Nlm Unique ID:  8205768     Medline TA:  J Cell Biochem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  345-57     Citation Subset:  IM    
Copyright Information:
Copyright 2004 Wiley-Liss, Inc.
Department of Anatomy and Cell Biology and UF Shands Cancer Center, College of Medicine, University of Florida, Gainesville, Florida 32610, USA.
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MeSH Terms
Adenomatous Polyposis Coli Protein / genetics,  metabolism*
Cadherins / metabolism
Caspase 3
Caspases / metabolism
Cell Cycle / drug effects*
Cell Line, Tumor
Cell Proliferation / drug effects
Cell Shape / drug effects
Chlorides / pharmacology*
Colonic Neoplasms / metabolism*,  pathology*
Cyclins / metabolism
Cytoskeletal Proteins / metabolism
G2 Phase / drug effects
Mitosis / drug effects
RNA, Messenger / genetics,  metabolism
Signal Transduction
Trans-Activators / metabolism
Zinc Compounds / pharmacology*
beta Catenin
Grant Support
R01 CA077721/CA/NCI NIH HHS; R01 CA097031/CA/NCI NIH HHS; R01-CA77721/CA/NCI NIH HHS; R01-CA97031/CA/NCI NIH HHS
Reg. No./Substance:
0/Adenomatous Polyposis Coli Protein; 0/CTNNB1 protein, human; 0/Cadherins; 0/Chlorides; 0/Cyclins; 0/Cytoskeletal Proteins; 0/RNA, Messenger; 0/Trans-Activators; 0/Zinc Compounds; 0/beta Catenin; 86Q357L16B/zinc chloride; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases

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